Process for arresting the proliferation of organisms that convert axillary secretions to malodorous materials
A process for arresting the proliferation of microorganisms which convert axillary secretions into malodorous materials by treating these axillary secretions with a composition containing a compound selected from the group consisting of tripelennamine, phenindamine, hexylcaine, tetracaine, naphazoline, xylometazoline, pyrilamine and pharmaceutically acceptable salts thereof.
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This invention relates to a process for arresting the proliferation of aerobic diphtheroids, staphylococci and micrococci which convert axillary secretions in a subject to malodorous materials. More particularly, it concerns a process of the aforesaid type in which the axillary secretions are apocrine gland secretions.
The art has long appreciated that axillary sweating is caused by two types of sweat glands; the eccrine sweat glands and the apocrine sweat glands. Products that are designed to inhibit perspiration are targeted to act on the eccrine sweat glands. The development of axillary odor, however, is thought to be primarily due to the action of the species of aerobic diphtheroids, staphylococci and micrococci on apocrine gland secretions.
It has now been found that the proliferation of representative species of aerobic diphtheroids, staphylococci and micrococci and the development of malodorous products due to the action of these organisms on apocrine sweat can be arrested by treating the secretion of the axilla of a subject with a material selected from the group consisting of tripelennamine, phenindamine, hexylcaine, tetracaine, naphazoline, xylometazoline, pyrilamine and pharmaceutically acceptable salts thereof (hereinafter referred to as the active material).
It has been suggested in the prior art to use certain antihistamines alone or in combination with astringent metallic salts for retarding or inhibiting perspiration. In this connection, see the U.S. Pat. Nos. 4,226,850 and 4,234,566 to Packman. In column 3 beginning at line 56 of each of these patents, the patentee discloses that the compositions of his invention use antihistamines to inhibit the secretion or excretion of substances which give rise to offensive odors.
It is clear from these teachings that Packman was concerned with inhibition of glandular secretions and not arresting the growth of organisms in axillary secretions and particularly, secretions from the apocrine glands as is characteristic of the present invention. Further, the test procedure used by the patentee is traditionally used only for measuring the inhibition of eccrine sweating as opposed to deodorancy. The above patents are devoid of any experimentation to demonstrate an effect of antihistamines on apocrine glands or secretions therefrom.
It has also been suggested in the prior art that certain antihistamines exhibit antimicrobial activity. Of interest in this regard are two literature references. One is an article by P. K. Saha et al entitled "Antimicrobial Activity of Antihistaminic Drugs" in the Indian J. Med. Res. 64, 11, November 1976, p. 1677-1679. The other is an article by the same authors in J. Appl. Bacteriol. 41, (2) 1976, p. 209-214. These papers are concerned with in vitro studies of the effect of certain antihistamines in a culture medium or in vivo studies in mice for treatment of certain infections. They are not concerned with arresting axillary odor development as is the case with the present invention. Furthermore, as is clear from these articles, there was great variation among the antihistamines tested regarding their antibacterial activity. Lastly, it is to be noted that the only materials used in this invention that can be characterized as antihistamines are tripelennamine, phenindamine, and pyrilamine and this was not disclosed in these literature references.
In the J. Clin. Pharm. Vol. 10, 1970, p. 235-246, Goodall describes a study in which certain adrenergic and cholinergic blocking agents were tested as sweat inhibiting agents. Among the compounds tested by Goodall for this purpose were tripelennamine HCl and phenindamine tartrate. However, there is no teaching in this reference that these materials are useful for inhibiting apocrine sweating or for arresting the proliferation of aerobic diphtheroids, staphylococci and micrococci in axillary secretion to prevent the formation of malodorous materials.
In practicing the process of this invention, the active material is applied to the axilla of the subject in which the axillary secretions and particularly apocrine sweat is present for sufficient time to arrest the proliferation of the axillary organism. The active material will generally be distributed in a vehicle that can bring it into contact with the axillary secretions. The quantity of active material that will be contained in the vehicle may vary somewhat. All that is required is that it be present in sufficient concentration in the vehicle so as to arrest the proliferation of said organism in the axillary secretions. Generally, said active material will be present in said vehicle in the range of from about 0.1% to about 10% by weight based on the total weight of the composition. In a preferred aspect of this invention, this concentration will be from about 1% to about 5% on the same weight basis.
Various vehicles may be used in accordance with the present invention. All that is required is that the active ingredient be soluble in or solubilized or suspended in the vehicle. Thus, the vehicle may be a simple solvent system, a cream, lotion, ointment, cosmetic stick, aerosol system, etc.
The following are typical examples of a variety of vehicles in which active materials employed in the present invention may be distributed. Any of the active materials mentioned above may be incorporated in these vehicles. The percentages indicated in the Examples below and elsewhere in this specification, unless otherwise specified, are percentages by weight based on the total weight of the composition.
______________________________________
% by Wt.
______________________________________
Deodorant Aerosol
Deodorant active 5.0
Propylene glycol 3.0
SD-40 Anhydrous alcohol
47.0
Fragrance 2.5
Isobutane QS to 100.0
Roll-On Lotion Deodorant
Carboxyvinyl polymer, 941
0.1500
Triethanolamine, 98%
0.0855
Disodium edetate, dihydrate
0.1000
Cetyl alcohol 0.5000
Glyceryl monostearate,
2.5000
non-self emulsifying
Deodorant active 5.0000
Isopropyl palmitate 2.0000
Mineral oil, 55-65 SUS
1.0000
Sodium lauroyl isethionate
0.5000
Glycerin, anhydrous 4.8120
Monomethylol dimethyl
0.2500
hydantoin
Perfume 0.3000
Water, deionized QS to
100.0000
Deodorant Stick
Propylene glycol 61.00
Sorbitol solution, 70%
5.00
Sodium stearate C-7 (Witco)
7.00
Color FD&C Yellow #6
0.12
(1.0% solution)
Deodorant active 5.00
Perfume 1.50
Water, deionized QS to
100.00
Deodorant Cream
Colloidal magnesium 1.4000
aluminum silicate, HV
Sodium phosphate, dibasic,
0.3500
anhydrous
Sodium hydroxide, pellets
0.0800
Carboxyvinyl polymer, 934
0.2000
Sorbitol solution, 70%
2.3000
Glycerin, anhydrous 2.8870
Isopropyl palmitate 3.6000
Partial sodium salt of
1.6000
N--lauryl-B--Iminopropionate
Lanolin, anhydrous 1.0000
Glyceryl monostearate,
2.7000
non-self emulsifying
Cetyl alcohol 1.2000
Deodorant active 5.0000
Stearic acid, T.P., flakes
13.0000
Monomethylol dimethyl
0.2500
hydantoin
Perfume 0.5000
Water, deionized QS to
100.0000
Deodorant Stick
Deodorant active 5.00
Stearyl alcohol 10.00
Castorwax MP 80 4.00
FT 300 Wax 2.00
Fluid AP 3.00
Ionol CP 0.05
Silicone 7158 44.95
Talc 5251 25.00
SD-50 Anhydrous alcohol
5.00
Brij 35 1.00
100.00
Deodorant Stick
Deodorant active 5.00
Stearyl alcohol 8.50
Castorwax MP 80 5.00
FT 300 Wax 2.00
Fluid AP 3.00
Ionol CP 0.05
Silicone 7158 51.45
Talc 5251 25.00
100.00
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The following Examples are given to further illustrate the present invention. It is understood, however, that the invention is not limited thereto.
EXAMPLE 1 (BO 1540-553) ______________________________________
Ingredients % by Wt.
______________________________________
Phenindamine tartrate
5
Sodium sulfate 20
Deionized water QS to
100
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EXAMPLE 2
(BO 1540-588)
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Ingredients % by Wt.
______________________________________
Tripelennamine HCl 5
Sodium sulfate 5
Deionized water QS to
100
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EXAMPLE 3
(BO 1540-768)
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Ingredients % by Wt.
______________________________________
Phenindamine tartrate
5
Deionized water 95
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To test the activity of the compounds employed in the present invention in arresting the proliferation of axillary organisms (e.g. corynebacteria and staphylococci) the following in vitro study was carried out:
Test ProcedureAqueous solutions (or suspensions) were prepared for each test substance. Serial two-fold dilutions of the above were then made in liquid culture medium. Each tube (10 ml of liquid) in the dilution series was inoculated with 0.2 ml of a 1:500 dilution of 24 hr. culture of bacteria. After 24 hrs. at 35.degree. C., tubes showing turbidity (growth) were noted. All non-turbid dilutions were subcultured to liquid growth medium and incubated an additional 24 hrs. at 35.degree. C. The lowest concentration of substance which yielded no growth upon subculture was noted as the minimum inhibitory (bactericidal) concentration (=MIC).
The results of this study are summarized in Table I below. The numbers appearing in columns 2 and 3 give the minimum inhibitory concentration in percent (MIC %) for the materials tested i.e. the minimum concentration in percent of the agent tested which will inhibit the proliferation of the test organisms. The entries in the last column are judgments with respect to the activity of the agent tested.
TABLE I
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In vitro Studies - Summary
MIC (%) - cidal
Staph
(Axilla)
Diphth (Axilla)
Comments
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Phenindamine
0.04 0.08 Good Activity
tartrate
Tripelennamine HCl
0.63 0.31 "
Naphazoline HCl
0.31 0.31 "
Xylometazoline HCl
0.08 0.04 "
Hexylcaine HCl
0.16 0.16 "
Tetracaine HCl
0.08 0.08 "
Pyrilamine 0.63 0.63 "
maleate
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Three in vivo studies were also carried out to further confirm the ability of the compounds employed in this invention to arrest the proliferation of axillary organisms in axillary secretions. In these studies, the criteria for effectiveness was taken as the ability of the agent to inhibit or neutralize axillary odor. The procedure and materials tested were as follows:
STUDY I Subjects12 Adult Males
Materials5% tripelennamine HCl in aqueous 5% sodium sulfate, BO 1540-588
MethodFollowing a control (or 24 hour) evaluation, both axillae were washed with Ivory soap and water. The test product was applied according to a randomly pre-assigned axilla allocation. Four panelists had product applied to the left axilla and eight to the right. The other axilla of each subject was left untreated to serve as a control. Odor evaluations were made 3, 6 and 24 hours later. The same procedure was repeated the second day.
Three judges were used for the study. An odor scale of 0-10 was employed for these observations with 0 indicating the absence of detectable odor and 10 very strong odor.
STUDY II Subjects16 adults (1 female, 15 males)
Materials5% phenindamine tartrate in aqueous 20% sodium sulfate (BO 1540-553)
MethodFollowing a control evaluation, both axillae were washed with Ivory soap and water. The test product was applied according to a randomly pre-assigned axilla allocation. The other axilla of each subject was left untreated to serve as a control. Odor evaluations were made at 3, 6, and 24 hours later. The same procedure was repeated the second day.
Three judges were used for the study. An odor scale of 0-10 was employed for these observations with 0 indicating the absence of detectable odor and 10 very strong odor.
STUDY III Subjects11 adult males
Materials5% phenindamine tartrate in aqueous 20% sodium sulfate (BO 1540-769)
5% phenindamine tartrate in water (BO 1540-768)
MethodFollowing a control evaluation, both axillae were washed with Ivory soap and water. The test products were applied according to a randomly pre-assigned axilla allocation. Odor evaluations were made at 3, 6, and 24 hours after the second product application.
Three judges were used for the study. An odor scale of 0-10 was employed for these observations with 0 indicating the absence of detectable odor and 10 very strong odor.
The results of these studies are summarized in Table II below.
TABLE II
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Deodorant Panel Results
Product Actives Excipients
Results
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Phenindamine
5% Phenindamine
20% Significant
Sol. tartrate sodium odor reduction
BO 1540-553 sulfate in
vs. untreated
(EXAMPLE 1) water
Tripelennamine
5% Tripelen- 5% sodium Significant
Sol. namine HCl sulfate in
odor reduction
BO 1540-588 water vs. untreated
(EXAMPLE 2)
Phenindamine
5% Phenindamine
water Significant
Sol. tartrate odor reduction
BO 1540-768 not different
(EXAMPLE 3) from Example 1
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Although the invention has been described with reference to specific forms thereof, it will be understood that many changes and modifications may be made without departing from the spirit of this invention.
Claims
1. A process for arresting the proliferation of aerobic diptheroids, staphylococci and micrococci which convert axillary secretions into malodorous materials, which comprises treating said axillary secretions in the axilla of a subject with a composition comprising a compound selected from the group consisting of hexylcaine, tetracaine, naphazoline, xylometazoline and pharmaceutically acceptable salts thereof.
2. A process according to claim 1 in which said composition comprises an aqueous composition containing said compound.
3. A process according to claim 1 in which said composition comprises a cream containing said compound.
4. A process according to claim 1 in which said composition comprises a lotion containing said compound.
5. A process according to claim 1 in which said composition comprises an ointment containing said compound.
6. A process according to claim 1 in which said composition comprises a cosmetic stick containing said compound.
7. A process according to claim 1 in which said composition comprises an aerosol composition containing said compound.
8. A process according to claim 1 in which said compound is present in said composition that the concentration is in the range of from about 0.1% to about 10% by weight based on the total weight of said composition.
9. A process according to any one of claims 1-8 in which said compound is naphazoline hydrochloride.
10. A process according to any one of claims 1-8 in which said compound is xylometazoline hydrochloride.
11. A process according to any one of claims 1-8 in which said compound is hexylcaine hydrochloride.
12. A process according to any one of claims 1-8 in which said compound is tetracaine hydrochloride.
| 2868802 | January 1959 | Hueni |
| 3312709 | April 1967 | MacMillan |
| 3326768 | June 1967 | MacMillan |
| 3527864 | September 1970 | MacMillan et al. |
| 3624200 | November 1971 | Moffett |
| 3767786 | October 1973 | MacMillan |
| 3775538 | November 1973 | DeSalva et al. |
| 3953599 | April 27, 1976 | MacMillan |
| 4010252 | March 1, 1977 | Hewitt |
| 4226850 | October 7, 1980 | Packman et al. |
| 4234566 | November 18, 1980 | Packman et al. |
- Saha, Indian Journal, Medical Research, 11/11/76, pp. 1677 to 1679.
Type: Grant
Filed: Jun 6, 1983
Date of Patent: May 3, 1988
Assignee: Bristol-Myers Company (New York, NY)
Inventors: Sydney M. Henry (Westfield, NJ), Gene Jacobs (Montclair, NJ), Val F. Cotty (Westfield, NJ)
Primary Examiner: Dale R. Ore
Attorney: Charles J. Zeller
Application Number: 6/501,306
International Classification: A61K 732; A61K 907; A61K 912;
